Useful Chemistry

This blog chronicles the research of the UsefulChem project in the Bradley lab at Drexel University. The main project currently involves the synthesis of novel anti-malarial compounds. The work is done under Open Notebook Science conditions with the actual detailed lab notebook located at usefulchem.wikispaces.com. More general comments posted here relate to Open Science, especially when associated with chemistry.

The presentations were recorded and should be available within a week on the wiki link above - I'll post an update here when I am made aware of it.

The take-home message for me resonated around the idea that there exists a group of really strong advocates for the Open Science movement. The actual tools, whether they be wikis, blogs, custom databases or open-source software, were secondary to the fundamental philosophy of openness.

The SciBarCamp breakout sessions were certainly very lively. Since we were mainly preaching to the choir, controversy was at a minimum. However we did acknowledge the difficulty in pursuing an Open Science agenda within the current establishment.

It was hard to resist pointing out the remarkable recent success of FriendFeed in facilitating communication between life scientists. Of course Deepak brought that up during his session.

The fact that this conference was organized and funded on such short notice is a testament to the commitment of the core Open Science group - thanks to John Wooley andSrikrishna Subramanian for making it happen!

SciFoo Preview Area

To kick things off, 23andMe will be presenting tomorrow June 24, 2008 at 10:00 PDT / 13:00 EDT/ 17:00 GMT on Second Nature island. Berci Mesko had already made arrangements for them to speak - and since they will be at SciFoo this is a convenient way to get things started.

Other SciFoo presenters coming soon...

The presentation area is next door to the SciFoo Lives On section: SLURL

New Communication Channels for Biology Workshop

I'll be attending the "New Communication Channels for Biology" Workshop at UCSD on Wednesday. It looks like it will be very intense and I hope to see a few people from the Open Science movement there!

The workshop will focus on the range of emerging approaches within e-science, community engagement in dialogue knowledge input/review or assessment, science blogs, and authenticated wiki-like research discussions and analysis, as well as the potential to formalize such community level contributions. These new approaches to communication are becoming important for biology as biological scientists attempt to address the inherent complexity of life, manage both high information content and high throughput data streams, and employ the opportunities emerging from advances in e-communication/networking and information technology. In part, this meeting has been stimulated by the success of the PSI KB Annotation Workshop, and by the general need within research both in metagenomics and structural genomics to understand the changing means of scientific communication and how we can best reach out to the community and have our work be enhanced in timely impact. The general case of getting input to genomic data from the entire community, third party annotation and not from only the original provider, is another driver for the need to extend communication beyond traditional publications, but the transformations in scientific dialogue / communication are much broader than just that within the genome community.

MiniBlock® is a flexible, easy to use tool designed for parallel synthesis. MiniBlock® is the only compact parallel synthesizer that allows synthesis via Solid Phase or Solution Phase to be carried out on the same platform. Originally designed by medicinal and combinatorial chemists at Bristol-Myers Squibb Company, the MiniBlock® has been further developed to address a wide range of chemistry methodologies.

Sunday, June 15, 2008

Ugi Reaction on MiniMapper - Trial 1 Preliminary Results

The idea here was to repeat a Ugi reaction known to work in methanol at 0.5M concentration (EXP099) and explore the experimental space varying solvent, concentration and an excess of some of the reagents.

All 48 reactions gave precipitate (EXP189). We still have to optimize the lighting and camera angle to see this clearly for all tubes:

In reviewing the results I noticed an inconsistency between the experimental design and the information in the GoogleDoc used to plan the details of the experiment. But because the MiniMapper stores the log of its actions in an XML log file, Khalid was able to make corrections to the worksheet.

Based on the weight of product and the limiting reagent, a yield for each reaction was calculated (column AC).

The best 4 yields (48-61%) were found for 4:1 acetonitrile/methanol solutions at the lowest concentration (0.1 M). It is counterintuitive that a multi-component reaction should work better at lower concentration but this is an effect that I noted previously.

Ironically, the absolute lowest yield (1.4%) was found for the 0.5M methanol reaction that was supposed to be the positive control!

This may be due to a malfunction in the delivery of one of the reagents. However, the other reactions carried out at this concentration in methanol were all low yielding (10-15%), compared to when it was run manually in EXP099 (37%).

I must stress that these results are very preliminary since we have not yet shown that the isolated materials are all pure Ugi products. As the NMRs come in I'll update the status.

But I think that this was a good first trial to demonstrate what kind of questions can be asked with the power of automation and the importance of reporting automated logs in Open Notebook Science.

Tuesday, June 10, 2008

Open Source Drug Discovery gets Funding

We've been successful in securing a large government grant with an open source component. The 3-year project concerns the enantioselective synthesis of PZQ for a low price, with the World Health Organisation as partner. (PDF of the Uni Sydney outcomes is here). The funding comes from the Australian Research Council (the main government funding agency in Australia). We wrote the proposal emphasising the possibilities inherent in the open source approach to doing science, and we're very pleased that this was seen as positive by an official grant-funding agency. The funding will allow us to increase our efforts on using TSL to drive our project forward much faster.

Drexel eCrysals Repository

Since we are operating under Open Notebook Science conditions, all of our structures will be made immediately available. However, the system is designed to allow contributors to select an embargo date if desired. Anyone from the Drexel community is welcome to participate.

For example, the record for one of our anti-malarial compounds UC-150D can be shared through a simple URL: http://ecrystals.chemistry.drexel.edu/1. The 3D structure of the molecule is displayed in an interactive Jmol JAVA applet with links to all the relevant raw data files. The record can also be cited with a formal author list, making it convenient to acknowledge our crystallography collaborator (Matthias Zeller) and students who contributed.

Note that the crystal structure file for this compound is also available on its ChemSpider entry. In a world of Open Distributed Science, redundancy is information's best friend.

Tuesday, June 03, 2008

Gates Submission on ONS, crowdsourcing and malaria

Creative, unorthodox thinking is essential to overcoming the most persistent challenges in global health. The first vaccines were developed over 200 years ago because revolutionary thinkers dared to try an entirely new approach to preventing disease.

The power of innovation is at work in countless other fields, from space travel to the Internet: now is the time to harness that power to save lives and improve the health of millions of people in the developing world.

Grand Challenges Explorations will foster innovation in global health research and expand the pipeline of ideas that merit further exploration. The initiative will use an agile, accelerated grant-making process with short two-page applications and no preliminary data required. Initial grants will be awarded multiple times per year at approximately $100,000 each. Additional funding of $1 million or more will be available for projects that show promise.

There is a 2 page limit so the proposal was painted in very broad strokes. Since Nature Precedings doesn't take proposals anymore, I just uploaded it to Noam Harel's SCIEnCE wiki. The core concept is leveraging crowdsourcing and Open Notebook Science to develop new anti-malarial agents. It is similar to the last NSF proposal I submitted, except that the purpose is squarely on drug development, which is not allowed for NSF funding.